Fatima_2023_Arch.Pharm.(Weinheim)__e2300384

A library of 22 derivatives of 1,3,4-oxadiazole-2-thiol was synthesized, structurally characterized, and assessed for its potential to inhibit alpha-amylase, alpha-glucosidase, acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and antioxidant activities. Most of the tested compounds demonstrated good to moderate inhibition potential; however, their activity was lower than that of the standard acarbose. Significantly, compound 3f exhibited the highest inhibition potential against alpha-glucosidase and alpha-amylase enzymes, with IC(50) values of 18.52 +/- 0.09 and 20.25 +/- 1.05 microM, respectively, in comparison to the standard acarbose (12.29 +/- 0.26; 15.98 +/- 0.14 microM). Compounds also demonstrated varying degrees of inhibitory potential against AChE (IC(50) = 9.25 +/- 0.19 to 36.15 +/- 0.12 microM) and BChE (IC(50) = 10.06 +/- 0.43 to 35.13 +/- 0.12 microM) enzymes compared to the standard donepezil (IC(50) = 2.01 +/- 0.12; 3.12 +/- 0.06 microM), as well as DPPH (IC(50) = 20.98 +/- 0.06 to 52.83 +/- 0.12 microM) and ABTS radical scavenging activities (IC(50) = 22.29 +/- 0.18 to 47.98 +/- 0.03 microM) in comparison to the standard ascorbic acid (IC(50) = 18.12 +/- 0.15; 19.19 +/- 0.72). The kinetic investigations have demonstrated that the compounds exhibit competitive-type inhibition for alpha-amylase, noncompetitive-type inhibition for alpha-glucosidase and AChE, and mixed-type inhibition for BChE. Additionally, a molecular docking study was performed on all synthetic oxadiazoles to explore the interaction details of these compounds with the active sites of the enzymes.